RESUMO
Deep learning may detect biologically important signals embedded in tumor morphologic features that confer distinct prognoses. Tumor morphologic features were quantified to enhance patient risk stratification within DNA mismatch repair (MMR) groups using deep learning. Using a quantitative segmentation algorithm (QuantCRC) that identifies 15 distinct morphologic features, we analyzed 402 resected stage III colon carcinomas [191 deficient (d)-MMR; 189 proficient (p)-MMR] from participants in a phase III trial of FOLFOX-based adjuvant chemotherapy. Results were validated in an independent cohort (176 d-MMR; 1,094 p-MMR). Association of morphologic features with clinicopathologic variables, MMR, KRAS, BRAFV600E, and time-to-recurrence (TTR) was determined. Multivariable Cox proportional hazards models were developed to predict TTR. Tumor morphologic features differed significantly by MMR status. Cancers with p-MMR had more immature desmoplastic stroma. Tumors with d-MMR had increased inflammatory stroma, epithelial tumor-infiltrating lymphocytes (TIL), high-grade histology, mucin, and signet ring cells. Stromal subtype did not differ by BRAFV600E or KRAS status. In p-MMR tumors, multivariable analysis identified tumor-stroma ratio (TSR) as the strongest feature associated with TTR [HRadj 2.02; 95% confidence interval (CI), 1.14-3.57; P = 0.018; 3-year recurrence: 40.2% vs. 20.4%; Q1 vs. Q2-4]. Among d-MMR tumors, extent of inflammatory stroma (continuous HRadj 0.98; 95% CI, 0.96-0.99; P = 0.028; 3-year recurrence: 13.3% vs. 33.4%, Q4 vs. Q1) and N stage were the most robust prognostically. Association of TSR with TTR was independently validated. In conclusion, QuantCRC can quantify morphologic differences within MMR groups in routine tumor sections to determine their relative contributions to patient prognosis, and may elucidate relevant pathophysiologic mechanisms driving prognosis. SIGNIFICANCE: A deep learning algorithm can quantify tumor morphologic features that may reflect underlying mechanisms driving prognosis within MMR groups. TSR was the most robust morphologic feature associated with TTR in p-MMR colon cancers. Extent of inflammatory stroma and N stage were the strongest prognostic features in d-MMR tumors. TIL density was not independently prognostic in either MMR group.
Assuntos
Neoplasias do Colo , Reparo de Erro de Pareamento de DNA , Aprendizado Profundo , Recidiva Local de Neoplasia , Microambiente Tumoral , Humanos , Neoplasias do Colo/patologia , Neoplasias do Colo/genética , Masculino , Recidiva Local de Neoplasia/patologia , Feminino , Pessoa de Meia-Idade , Idoso , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Compostos Organoplatínicos/uso terapêutico , Quimioterapia AdjuvanteAssuntos
COVID-19/diagnóstico , Portador Sadio/diagnóstico , Ensaios Clínicos como Assunto , Oncologia , Neoplasias/terapia , COVID-19/imunologia , Teste de Ácido Nucleico para COVID-19/métodos , Proteínas do Envelope de Coronavírus/genética , Proteínas do Nucleocapsídeo de Coronavírus/genética , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia Adotiva/métodos , Neoplasias/imunologia , Participação do Paciente , Fosfoproteínas/genética , SARS-CoV-2 , Sensibilidade e EspecificidadeRESUMO
The North Central Cancer Treatment Group (NCCTG) was founded in 1977 as a regional cooperative group to allow cancer patients in the upper Midwest of the United States to gain access to clinical trials in oncology by establishing a network of community oncology practices with one academic research base, the Mayo Clinic. Since then, the NCCTG has grown into an international cooperative group with 43 members in 33 US states and Canada. This article details 30 years of achievements of the NCCTG, including important scientific contributions from disease-specific and treatment modality committees, the cancer control program, patient-reported outcomes and quality-of-life research, and biostatisticians that support the NCCTG's specific aims: to improve the duration and quality of life of cancer patients, to enhance our understanding of the biological consequences of cancer and its treatment, and to improve methods for clinical trial conduct.